Margaritis Laboratory

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Research in the Margaritis Lab uses basic biochemical, molecular, and complex in vivo methodology within the field of coagulation. The lab’s goals are to advance the understanding of molecular mechanisms involved in pro- and anti-coagulant reactions, and conduct translational research for the treatment of coagulation defects. Despite their different endpoints, these goals exhibit remarkable cross talk since answering mechanistic questions on coagulation impacts the design of therapeutic approaches for coagulation defects.

The lab’s research pivots on a unique model it developed that involves enhancing the extrinsic pathway of coagulation by raising the circulating levels of activated FVII (FVIIa) in animal models. In a series of novel experiments on hemophilia, the lab showed that expression of FVIIa via gene transfer results in dramatic phenotypic improvements or complete correction.

In addition, the Margaritis Lab developed mouse- and canine-specific reagents, assays, and endpoints that allow for monitoring of in vivo effects in hemostasis resulting from the action of FVIIa. A current line of investigation in the laboratory aims to better define the intricacies of viral transduction-based FVIIa gene expression and its hemostatic effects in animal models of hemophilia.

In addition, part of ongoing work in the Margaritis Lab is a new line of investigation that focuses on the molecular interactions between FVIIa and its binding partners and how these relate to the hemostatic and other role(s) of FVIIa in vivo. To address these functions the lab developed unique in vitro and in vivo methodologies to define, quantitate and even visualize FVIIa-participating reactions as they occur in real time. Exploiting this information may also form the basis for the rational design FVIIa-based therapeutics, either protein or gene-based, that can be used for the treatment of coagulation defects.

Leader

Paris Margaritis, DPhil

Investigator
Dr. Margaritis uses biochemical, molecular, and complex in vivo methodology within the field of coagulation to advance the understanding of molecular mechanisms involved in pro- and anti-coagulant reactions, and translate research for the treatment of coagulation defects.